Abstract
Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung condition. It is characterized by disruption of gas exchange inside the alveoli, accumulation of protein edema, and an increase in lung stiffness. One major cause of ARDS is a lung infection, such as SARS-COV-2 infection. Lungs of ARDS patients need to be mechanically ventilated for airway reopening. Consequently, ventilation might damage delicate lung tissue leading to excess edema, known as ventilator-induced lung injury (VILI). Mortality of COVID-19 patients under VILI seems to be higher than non-COVID patients, necessitating effective preventative therapies. VILI occurs when small air bubbles form in the alveoli, injuring epithelial cells (EPC) due to shear stress. Nitric oxide (NO) inhalation was suggested as a therapy for ARDS, however, it was shown that it is not effective because of the extremely short half-life of NO. In this study, NO-releasing nanoparticles were produced and tested in an in vitro model, representing airways in the deep lung. Cellular injuries were quantified via fluorescent live/dead assay. Atomic force microscopy (AFM) was used to assess cell morphology. qRT-PCR was performed to assess the expression of inflammatory markers, specifically IL6 and CCL2. ELISA was performed to assess IL6 and confirm qRT-PCR results at the protein level. Finally, ROS levels were assessed in all groups. Here, we show that NO delivery via nanoparticles enhanced EPC survival and recovery, AFM measurements revealed that NO exposure affect cell morphology, while qRT-PCR demonstrated a significant downregulation in IL6 and CCL2 expression when treating the cells to NO both before and after shear exposure. ELISA results for IL6 confirmed qRT-PCR data. ROS experiment results support our findings from previous experiments. These findings demonstrate that NO-releasing nanoparticles can be used as an effective delivery approach of NO to deep lung to prevent/reduce ARDS associated inflammation and cell injuries. This information is particularly useful to treat severe ARDS due to COVID-19 infection. These nanoparticles will be useful when clinically administrated to COVID-19 patients to reduce the symptoms originating from lung distress.
Highlights
Acute respiratory distress syndrome (ARDS) is a clinical condition that is characterized by increased permeability of pulmonary/capillary barrier in the gas exchange sites in the lung, resulting in the accumulation of edema fluid and hypoxia in the lung (Koh, 2014)
Presence of edema fluid results in the inactivation of the surfactant molecules in the thin liquid layer over the epithelial cells. This layer acts to protect the cells by decreasing surface tension and in diseased lungs, as a result of inactivation of these molecules, epithelial cells become prone to injury
Mechanical ventilation can induce overdistension of gas exchange sites resulting in propagation of small bubbles in terminal bronchioles and alveoli, resulting in exposure of shear stress to the epithelial cells (EpCs)
Summary
Acute respiratory distress syndrome (ARDS) is a clinical condition that is characterized by increased permeability of pulmonary/capillary barrier in the gas exchange sites in the lung, resulting in the accumulation of edema fluid and hypoxia in the lung (Koh, 2014). Presence of edema fluid results in the inactivation of the surfactant molecules in the thin liquid layer over the epithelial cells. Mechanical ventilation can induce overdistension of gas exchange sites resulting in propagation of small bubbles in terminal bronchioles and alveoli, resulting in exposure of shear stress to the epithelial cells (EpCs). These mechanical forces might induce further injury to the already diseased tissue, a phenomenon known as ventilator-induced lung injury (VILI) (Biehl et al, 2013)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call